Approximately eighty percent of patients with rheumatoid arthritis (RA) make antibodies directed to an antigen termed RA nuclear antigen (RANA) which is associated with an Epstein-Barr virus (BBV) infection. Purification of RANA is of vital importance and is outlined in this proposal. Sensitive assays for detection of RANA or its antibody are central to various future studies and are also planned in this proposal but purified antigen is necessary to initiate these studies. Elucidation of the function of RANA in BBV infected RA cells is also imperative. For these studies we plan to use spontaneously transformed B lymphocyte lines started from patients with RA as models to begin to understand virus-host relationships. However, before more complicated studies can be performed we first must determine whether RA cell lines are BBV producer or non-producer lines. If some (or all) are non-producer lines they will be treated with DNA inhibitors to induce BBV replication and determine if they are capable of complete or abortive cycles. Once RA lines have been classified we will use various drugs to manipulate the virus-host relationships to begin to understand the function of RANA and possibly reduce its production.